Altered expression of γ-secretase components in animal model of major depressive disorder induced by reserpine administration.

1Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.

Abstract

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of γ-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of γ-secretase components decreased (P<0.03). Among the three components of the γ-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

KEYWORDS:

Behavioral changes in reserpine-induced MDD mice. ICR mice were administrated saline or reserpine (1 or 2 mg/kg) for 15 days. Altered behavioral performance in ICR mice was measured using active avoidance test as described in Materials and Methods. (A) Total response time was calculated from 30 randomized escapable footshocks, each at an intensity of 0.25 mA. (B) Response peak indicates the time spent in one half of the shuttle boxes. Data represent the mean±SD from three replicates. *P<0.05 is the significance level compared to the vehicle-treated group.

Expression of total and phosphorylated MKP-1 in brain cortex of reserpine-induced MDD mice. The cortex region was prepared from brain tissues of vehicle- and reserpine-treated mice. Fifty micrograms of protein per sample was immunoblotted with antibody for each protein. Expression levels of total and phosphorylated MKP-1 were detected using anti-MKP-1 and p-MKP-1 primary antibodies and horseradise peroxidase-conjugated goat anti-rabbit IgG (A). The intensity of each protein was calculated using an imaging densitometer (B). Data represent the mean¡¾SD from three replicates. *P<0.05 is the significance level compared to the vehicle-treated group.

Expression of γ-secretase components in brain tissues of reserpine-induced MDD mice. The cortex region was prepared from brain tissues of vehicle- and reserpine-treated mice. Fifty micrograms of protein per sample was immunoblotted with antibody for each protein. Expression levels of full-length APP and γ-secretase components were detected using specific antibody and horseradish peroxidase-conjugated goat anti-rabbit IgG (A). The intensity of each protein was calculated using an imaging densitometer (B). Data represent the mean¡¾SD from three replicates. *P<0.05 is the significance level compared to the vehicle-treated group.